Genomic analysis of multiple myeloma using targeted capture sequencing in the Japanese cohort

概要

Previous genomic studies have revealed the genomic landscape of myeloma cells. Although several studies have demonstrated the difference in tumor pathogenesis in non-hematological malignancy based on the racial and ethnic background of the patient the racial disparities in the hematological malignancies, including MM, are not well understood. There are limited studies which have focused on the genomic disparities in MM and suggested the presence of genetic heterogeneity between MM racial groups such as the Caucasian American population and the African American population. Besides, several studies indicate the presence of some racial differences in the genetic basis of MM in the Asian population, which may be useful for understanding the differential mechanism underlying MM pathogenesis and treatment efficacy in different racial groups. In this study, we investigated the genomic features of the Japanese cohort to evaluate the genomic alterations of MM in the Asian population. We analyzed 154 patients with newly diagnosed multiple myeloma. The analysis revealed that the study cohort consisted of a less frequent hyperdiploid subtype (37.0%) with relatively high frequencies of KRAS mutation (36.4%) and IGH-CCND1 translocation (26.6%) compared with previous reports. Moreover, our targeted capture sequencing strategy was able to detect rare IGH-associated chromosomal translocations, such as IGH-CCND2 and IGH-MAFA. Interestingly, all 10 patients harbored MAX mutations accompanied by 14q23 deletion. The patients with del(17p) exhibited an unfavorable clinical outcome, and the presence of KRAS mutation was associated with shorter survival in patients with multiple myeloma, harboring IGH-CCND1. Thus, our study provides a detailed landscape of genomic abnormalities, which may have potential clinical application for patients with multiple myeloma.